Geometry encoded functional programming of tumor homing peptides for targeted drug delivery

Poly-peptide molecules have shown promising applications in drug delivery and tumor targeting. A series of tumor homing peptides were designed by exhaustively sampling low energy geometrical basins of amino acids at specific sites of a peptide molecule to induce a conformational lock. This peptide l...

Celý popis

Uložené v:
Podrobná bibliografia
Vydané v:Journal of controlled release Ročník 333; s. 16 - 27
Hlavní autori: Goyal, Ruchika, Jerath, Gaurav, Akhil, R., Chandrasekharan, Aneesh, Puppala, Eswara Rao, Ponneganti, Srikanth, Sarma, Anupam, Naidu, V.G.M., Santhoshkumar, T.R., Ramakrishnan, Vibin
Médium: Journal Article
Jazyk:English
Vydavateľské údaje: Netherlands Elsevier B.V 10.05.2021
Predmet:
apoptosis
breast neoplasms
Cancer therapy
caspase-3
confocal microscopy
cytotoxicity
Drug design
drugs
energy
epithelium
flow cytometry
fluorescence
geometry
Heterochiral peptides
humans
membrane potential
mitochondrial membrane
molecular dynamics
osteosarcoma
peptide libraries
RGD motif
Targeted drug delivery
uterine cervical neoplasms
RGD motif
Heterochiral peptides
Targeted drug delivery
Drug design
Cancer therapy
ISSN:0168-3659, 1873-4995, 1873-4995
On-line prístup:Získať plný text
Tagy: Pridať tag
Žiadne tagy, Buďte prvý, kto otaguje tento záznam!
Popis
Shrnutí:Poly-peptide molecules have shown promising applications in drug delivery and tumor targeting. A series of tumor homing peptides were designed by exhaustively sampling low energy geometrical basins of amino acids at specific sites of a peptide molecule to induce a conformational lock. This peptide library was pruned to a limited set of eight molecules, employing electrostatic interactions, docking, and molecular dynamics simulations. These designed and optimized peptides were synthesized and tested on various cell lines, including breast cancer (MDA-MB-231), cervical cancer (HeLa), osteosarcoma (U2-OS), and non-cancerous mammary epithelial cells (MCF-10A) using confocal microscopy and flow cytometry. Peptides show differential uptake in cancerous MDA-MB-231, HeLa, U2-OS, and non-cancerous MCF-10A cells. Confocal imaging verified their ability to penetrate even in 3D tumorospheres of MDA-MB-231 cells. Further, experiments of mitochondrial membrane potential depolarization and Caspase-3 activation confirmed that their cytotoxic effects are by apoptosis. Homing ability of the designed peptides in in vivo system and fluorescence imaging with clinical samples of human origin have further confirmed that the in vitro studies are qualitatively identical and quantitatively comparable in their ability to selectively recognize tumor cells. Overall, we present a roadmap for the functional programming of peptide-based homing and penetrating molecules that can perform selective tumor targeting. [Display omitted] •Conformational locking of RGD peptides•Cellular targeting in cancer; Peptide-based drug delivery•Peptide-based drug delivery
Bibliografia:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ISSN:0168-3659
1873-4995
1873-4995
DOI:10.1016/j.jconrel.2021.03.010